Pharmacology

Question 1

NSAIDs

Answer 1

• non-steroidal anti-inflammatory drugs
• mechanism: inhibition of cyclooxygenase = inhibition of prostaglandins
• main effects: anti-inflammatory
• effect on kidneys: inhibits PG-related afferent arteriole vasodilation, can cause a decrease in GFR
• effect on micturition: inhibits PG-related contraction of the bladder, can lead to urinary retention
• associated with nephrotoxic AKI

Question 2

Prostaglandins do what to the afferent arteriole? What does this do to the GFR?

Answer 2

• vasodilate

- GFR is increased as a result

Question 3

ACE Inhibitors

Answer 3

• mechanism: inhibition of ACE, resulting in inactive angiotensin II: failure to vasoconstrict & failure to activate RAAS
• main effects: keeps BP low
• effect on kidneys: inhibits efferent arteriole vasoconstriction, can cause a decrease in GFR
• associated with nephrotoxic AKI

Question 4

What does angiotensin II do?

Answer 4

• causes systemic vasoconstriction (including the efferent arteriole) to increase GFR
• activates vasopressin secretion
• activates aldosterone secretion
• increases thirst
• these all result in increased fluid/BP

Question 5

Gentamicin

Answer 5

• an aminoglycoside antibiotic used for complicated UTIs
• mechanism: inhibits protein synthesis of bactera
• associated with nephrotoxic AKI

Question 6

Frusemide

Answer 6

• loop diuretic, acts on the thick-ascending limb
• mechanism: blocks Na-K-2Cl cotransporters, preventing reabsorption of Na+, K+, and Cl-
• main effects: promotes large fluid loss, decreases work load of heart (used in heart failure); loss of H2O, Na+, K+, and Cl-
• diuretics are associated with nephrotoxic AKI

Question 7

Thiazide

Answer 7

• diuretic, acts on the early distal tubule
• mechanism: blocks Na-Cl cotransporters, preventing reabsorption of Na+ and Cl-
• main effects: promotes fluid loss, keeps BP low; loss of H2O, Na+, and Cl-
• blocking Na-Cl cotransporters results in increased reabsorbtion of Ca2+ –> hypercalcemia is possible
• diuretics are associated with nephrotoxic AKI

Question 8

Cephalexin

Answer 8

• antibiotic used to treat UTI
• is a beta-lactam effective against gram + and some gram - strains
• used when there is a mild penicillin allergy

Question 9

Which antibiotic is commonly used in patients with a mild allergy to penicillin?

Answer 9

• Cephalexin
• however, 35% of people who are allergic to penicillin are also allergic to cephalexin, so only use cephalexin if the allergy is MILD

Question 10

Fluoroquinolone (Norfloxacin)

Answer 10

• an antibiotic used for UTI
• prevents DNA unwinding
• broad spectrum and has good tissue penetration
• 2 major (but rare) side effects: peripheral neuropathy & Achilles tendon rupture

Question 11

Nitrofurantoin

Answer 11

• an antibiotic used for UTI
• damages DNA
• has a low rate of bacterial resistance
• poor tissue penetration

Question 12

Why is Nitrofurantoin not recommended for pyelonephritis or prostatitis?

Answer 12

• because it has poor tissue penetration

Question 13

Trimethoprim & Sulfamethoxazole

Answer 13

• antibiotics used for UTI
• interfere with thymidine synthesis
• used together to reduce resistance growth

Question 14

What syndrome is Sulfamethoxazole associated with?

Answer 14

• Stevens Johnson’s Syndrome occurs if you’re allergic to the drug

Question 15

Amoxicillin & Clavulanic Acid

Answer 15

• antibiotics used for UTI
• beta-lactam
• used together for strains that are amoxicillin resistant

Question 16

What’s the mechanism behind the combined Amoxicillin and Clavulanic acid treatment?

Answer 16

• bacteria that produce beta-lactamase are resistant to amoxicillin, so we add clavulanic acid (inhibits beta-lactamase production) when fighting these strains

Question 17

5 Nephrotoxic Mechanisms

Answer 17

• altered glomerular hemodynamics
• tubular cell toxicity
• immune-mediated
• rhabdomyolysis
• crystal nephropathy

Question 18

Acetazolamide

Answer 18

• increases bicarbonate excretion
• mechanism: inhibits carbonic anhydrase, preventing bicarbonate’s conversion into CO2 (and H2O), thus preventing its reabsorption = increased secretion

Question 19

Amiloride

Answer 19

• K+ sparing diuretic; acts on the distal tubule & cortical collecting duct’s principal cells
• mechanism: blocks ENaC (luminal passive Na+ channels)
• main effects: promotes fluid loss; keeps BP low
• without Na+ moving into the cell, the lumen stays positive, so K+ can now move into the cell instead of being pushed out (allows it to be reabsorbed, hence K+ sparing)

Question 20

Spironolactone

Answer 20

• K+ sparing diuretic
• mechanism: binds to intracellular mineralocorticoid receptors, preventing aldosterone from doing so
• effect: no aldosterone = decreased Na+ reabsorption (& K+ secretion) = increased fluid loss
• may cause hyperkalemia

Question 21

Metformin

Answer 21

• an anti-diabetic drug
• mechanism: suppresses glucose production by the liver
• major risk: lactic acidosis (anaerobic respiration kicks in when glucose production is limited); the kidney can get rid of most of the acid, but in the context of dehydration (diarrhea, etc.), acidosis can rapidly occur